Pharmaceutical firm Eli Lilly recently announced that it would halt clinical tests for an experimental Alzheimer treatment. The drug’s failure was extremely disappointing, as it represented one of only five Alzheimer’s drugs under development to have even reached late-stage clinical trials.

Lilly’s announcement exemplifies the long odds that most drug researchers face in trying to identify cures for the world’s most debilitating diseases.

What needs to be addressed are the twin issues of drug development and regulatory science. Both are lagging.

Too many drug trials — almost 50 percent — are failing in the Phase III trial stage, the latest one because they are mired in regulatory treacle. This is an unsustainable economic model from an R&D standpoint, and the impact of Alzheimer’s on patients, their families, and American healthcare is devastating.

Better, more current and predictable scientific research and standards must be developed and devoted to streamlining the critical path. Investment in basic research is not enough. Specifically, new development tools, such as biomarkers, microarrays and other diagnostic tools, are needed to improve the predictability of the drug-development cycle and to lower the cost of research by helping industry identify product failures earlier in the clinical trials process.

A quarter-century ago, the success rate for a new drug used was about 14 percent. Today, a new medicinal compound entering Phase 1 testing — often after more than a decade of preclinical screening and evaluation — is estimated to have only an 8 percent chance of reaching the market. For very innovative and unproven technologies, the probability of a product’s ability to make it to the market is even lower. We must work together to turn that around.

When Thomas Edison was asked why he was so successful, he responded, “Because I fail so much faster than everyone else.” Consider the implications if the FDA could help companies fail faster. Using the lower end of the Tufts University estimate of the average pre-tax cost of new drug development, $802 million:

A 10 percent improvement in predicting failure before clinical trials could save $100 million in development costs.

Shifting 5 percent of clinical failures to Phase 1, the earliest stage, from Phase 3, the latest stage, reduces out of pocket costs for developers by $15-$20 million.

Shifting of failures to Phase 1 from Phase 2, the middle stage, would reduce their out of pocket costs by $12-$21 million.

All of these dollars could then be reinvested in other innovative development programs for new life-saving medicines.

For all that modern science has to offer, developing new treatments is still very much an art, in which hunches, intuition, and luck play a critical role. The odds are long. But for more medicine that is affordable and innovative, we need up-to-date regulations that compliment the drug trial process in order to take these chances, which is precisely the mission of the FDA’s moribund Reagan-Udall Foundation. The failure of Congress to free-up the seed funding the foundation has called for in the 2007 FDA Amendments Act must be corrected.

Senator Ted Kennedy said the Reagan-Udall Foundation “will make new research tools and techniques available to the entire research community, shortening the time it takes to develop new drugs and reducing costs for patients.”

Shortly before his death, I had the privilege of a private meeting with Nobel Laureate Joshua Lederberg. The topic of conversation was the future of the FDA and the agency’s Critical Path initiative. We talked about the state of applied research, the prioritization of development science, biomarkers, and a host of other future-oriented issues. He talked. I took a lot of notes.

At the end of the meeting, he put everything into perspective in a single sentence. He leaned over the table and said, “The real question should be, is innovation feasible?”

One more day — or week, or month, or perhaps even a year. It may not seem like much time, but patients with incurable cancer know better. For Christi Turnage of Mississippi, who lives with stage IV breast cancer, it means seeing her daughter start kindergarten, celebrating her 27th wedding anniversary, and watching her sons graduate from college.

Her family and her oncologist credit her quality of life for the past two years to the drug Avastin, a biologic that combats cancer by cutting off the blood supply to tumors. But advanced breast cancer patients like Turnage have been forced to spend precious time battling something else: the possibility that federal regulators will vote today to remove approval of Avastin for their treatment.

If officials with the U.S. Food and Drug Administration are wise, they will overrule the agency’s cancer-drug advisory panel, which voted 12-to-1 last month to recommend denying a valuable clinical option to advanced breast cancer patients. According to the Department of Health and Human Services, an estimated 40,000 women die from breast cancer each year.

The panel concluded that the costly drug doesn’t eke out enough extra lifetime among breast cancer patients to justify its use and risks. This ignores all the “super responders” — the patients who reap significant benefits from Avastin. Scientists have no way of identifying these people in advance, and they could be devastated if they are denied the medicine.

“This is not a worthless drug by any means,” Eric Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston. “There is almost certainly a group of women who get a big benefit.”

Indeed, the Susan G. Komen for the Cure and Ovarian Cancer National Alliance – recently sent a joint letter to the FDA urging the government to keep it as a choice best made by a woman and her doctor.

The groups also warned that if the FDA de-lists Avastin for breast cancer, it would only discourage future drug development.

Two years ago, the FDA fast-tracked approval of Avastin for metastatic breast cancer two years ago, and since then it has been prescribed to about 17,500 women a year with the disease. The drug, which earned FDA approval for the treatment of colon, lung, kidney and brain cancer, is the world’s best-selling cancer drug.

A clinical trial that took place from December 2001 and May 2004 found that Avastin boosted the amount of time that breast cancer patients lived without the disease spreading or worsening. The drug in combination with chemotherapy delayed tumor growth for about 11 months, which was more than five months longer than chemo alone. Follow-up studies indicated a less robust response, yet still found an average delay in tumor growth to between one and three months.

But even if Avastin does not, “on average,” extend life for breast cancer patients, that “average” is composed of patients who respond in dramatically different ways –including some like Christi Turnage who gain years.

Another is retired California art teacher Patricia Howard, who reports that infusions of Avastin every three weeks over the past two years have shrunk tumors in the lining of her lung and eliminated fluid that hampered her breathing. Now she enjoys shopping and golf, and describes her life as “beyond fabulous.”

Serving as a patient representative at the FDA’s last session, Howard recalled, “One doctor got up during the meeting and said ‘This drug gets women only to first base and we want a home run.’ I felt like jumping up and saying I don’t mind just being in the ballgame.”

If the FDA does remove approval of Avastin for breast cancer, doctors conceivably could write prescriptions for it anyway, going “off label.” But it’s likely that Medicare and private insurers would not cover the cost of what is one of the world’s most expensive drugs. Patients could continue Avastin only if they could afford $8,000 a month out of pocket.

Avastin is a better alternative than the status quo for breast cancer patients, and can be truly transformative for some. No wonder Avastin-users are desperately writing letters, circulating petitions and, like Turnage’s 19-year-old son Josh, posting videos on YouTube pleading their case.

Avastin is their last hope. The FDA should make sure it is not their lost hope.

The following is a guest post by Peter Pitts, president of the Center for Medicine in the Public Interest and a former FDA Associate Commissioner. The opinions expressed are his own.

As if Michigan didn’t already have enough economic troubles, here’s one more they can add to the list: last month, the University of Michigan announced that it will ban any industry sponsored continuing medical education (CME).

Why? In order “to dispel the risk or appearance of conflict of interest.” And from whom does the university feel it is necessary to distance themselves? From pharmaceutical and medical device companies who want to teach physicians about new and innovative medicines and technologies.

But in cash-strapped Michigan, where libraries are being shut and teachers are losing their jobs, the university can’t afford to reject any kinds of funding. In fact, the Fighting Wolverines currently receive about $1,000,000 for such services from drug and device manufacturers for continuing medical education.

The ban will also reduce the number of CME courses offered at the university. According to the Accreditation Council for Continuing Medical Education, the university produced 499 CME activities last year, which reached more than 130,000 physicians with important information about 21st century medical practice. The result will likely be less knowledge at a time when knowledge is power.

So, how will the university make up for this lack of funding? Does it expect the taxpayers of Michigan to make up the difference? Unfortunately, this question has been neither asked nor answered. In the quest for academic purity, both physicians and patients have been left out in the cold.

Researchers from the Cleveland Clinic published a paper in January that delved into whether or not support from the drug and device industries created a perception of bias in continuing medical education. After analyzing information from 95,429 physicians who participated in 346 CME activities of various types, they found it did not.

A similar position was taken by the American Association of Clinical Endocrinologists and the American College of Endocrinology who determined that there is no conflict of interest in the working relationships of physicians with the medical and pharmaceutical industries or the government. Rather, according to both organizations, there is a “commonality of interest” in the relationships that is healthy, desirable and beneficial. Indeed, the collaborative relationship among all three parties has resulted in many medical advancements and improved health outcomes like having fewer preventable diabetic amputations.

Having an “interest” is not necessarily a bad thing — as long as you’re transparent about it. And that’s something for the folks in Michigan to consider.

After a feisty year of debate, Congress has passed healthcare reform legislation. Once enacted, it will increase the number of Americans with health insurance as well as both the size and scope of government.

And the numbers? Staggering when you consider they are absurdly under-scored. According to Douglas Holtz-Eakin (director of the Congressional Budget Office from 2003 to 2005), if you strip out all the gimmicks and games and rework the calculus, a wholly different picture emerges: The health care reform legislation would raise, not lower, federal deficits, by $562 billion. Even with readjustment, it will make the Social Security trust fund look like Fort Knox.

So here’s the good news — the solution is innovation.

We have to embrace innovative technologies for medical records and prescribing. We need innovative clinical trial designs and molecular diagnostics so that we can develop better, more personalized medicines faster and for far less than the current $1 billion plus delivery charge. We need innovation in access and reimbursement policies that reward speed-to-best-treatment rather than more lower-cost patients per hour.

Will more people have access to health insurance? They will, and that’s a good thing. But, let’s be honest, we’re not talking about erasing the word “uninsured” from the American healthcare dictionary — we’re just redefining what it means.

We have to embrace the fact that we will all pay more in taxes (yes, all of us) eventually. And, ultimately, we will be okay with that. Americans are always willing to do what’s right for their fellow citizens. As Winston Churchill said, “Americans always want to do the right thing — after they have tried everything else.” Even so, many of our fellow Americans will receive less comprehensive healthcare benefits than they are receiving now.

So we’d better start taking innovation — of both the incremental and discontinuous varieties — seriously. And that means both spending more on harder developmental R&D (with concomitant higher investment risks). In this regard, the new legislative language on the development of FOBs (follow-on biologics or, if you prefer, biosimilars) is a good thing.

There’s lip service to the need for more robust comparative effectiveness — although this is a battle yet to be either defined (comparative effectiveness or cost effectiveness or clinical effectiveness?) or fought (do we need a U.S. version of NICE?). And a battle royal it will be. In addition, there’s as yet-to-be reconciled language on a Medicare advisory board that could very well morph into a national formulary body.

Of course we bid adieu to the infamous Medicare Part D Doughnut Hole. The Medicare prescription drug benefit is coming in hundreds of millions of dollars under budget already and consistently has 90-percent-plus approval ratings by America’s savvy seniors. Medicare Advantage programs? Don’t ask.

Now insurance companies can’t turn anyone down because of a pre-existing condition (bravo!) but they can’t charge higher premiums for people who have them? This isn’t an elegant or economically viable solution and will have to change. Otherwise it’s just a slow march to a single-payer system.

Over the past year, we spent a lot of wasted time throwing around terms like “death panels,” but at the end of the day, we didn’t even begin to address the elephant-in-the-room issue of how much of our national treasure we spend on end-of-life care. We will have to address this highly volatile and divisive issue — and sooner rather than later.

The legislation doesn’t do anything really significant about driving young, healthy people into the insurance pool. The anemic penalties (which don’t even kick-in right away — the demographics and politics aren’t too hard to figure out) actually disincentivize youthful participation. After all, why not pay the monthly penalty (which is less than even a very affordable monthly insurance premium) if, when you do face a medical emergency, you can’t be turned down or charged more?

Some of the best things about the bill are what is does not do.

No drug importation. (Sorry! Senator Dorgan. Hooray! Peggy Hamburg.) And the Non-Interference Clause remains the law of the land. When originally drafted (wisely by then-Senators Daschle and Kennedy), we knew then what we need to remember now, that (1) direct government negotiations for Medicare drug prices won’t (according to numerous government studies and leading economists) lower Medicare drug prices and (2) it is the next slippery step towards even broader price controls. And price controls equal choice controls.

So let’s keep our eye on the prize: better access to health care for all Americans and innovation that focuses on prevention and prophylactic care. We will not survive as a nation of obese, hypertensive diabetics. Rather than wasting time on spin, let’s redouble our efforts on innovation. Then, when we succeed through brainpower and teamwork (and hopefully some civil bipartisanship), the circus surrounding this vote and the past year’s partisan political warfare will be but a footnote in American political history.

Today, the Congressional Budget Office released its latest estimate of the price tag of the Democrats’ health reform package. At $940 billion, this version of reform will cost more than the measures passed by the House and Senate late last year. More is not always better.

CBO also says the bill will reduce the deficit by $130 billion over the next 10 years and by $1.2 trillion over the following decade. That’s right. It will reduce the deficit by significantly increasing federal spending. Only in America.

While they’re at it, they should also predict the weather for the next decade.

Let’s face it: Uncle Sam has a poor track record of forecasting how much new programs will cost. Medicare’s progenitors, for example, stated in 1967 that the entitlement would cost $12 billion by 1990. Actual Medicare spending in 1990 amounted to $110 billion — nearly 10 times the initial estimate. Oops.

CBO’s deficit-reduction estimates are further divorced from reality because they don’t include as much as $371 billion in new spending to fix reimbursement rates for doctors who treat Medicare patients. Imagine that — health reform legislation that doesn’t include payments to doctors. Only in Washington, DC.

Absent congressional action, Medicare reimbursement rates will fall 21 percent next year. Congress has no intention of letting that happen. But the Democrats have decided that they don’t have to include this so-called “doctor fix” in their healthcare reform package — even though it’s critical to preserving Medicare.

No wonder the CBO was able to conclude that the Democrats’ health reform package would reduce the deficit by $130 billion. The bean-counters simply ignored the $371 billion in spending needed to fix Medicare reimbursement rates.

Democrats point to the favorable CBO score as proof that their health reform package is a model of fiscal responsibility. But it’s likely that the next generation of lawmakers will look back on these cost estimates with the same astonishment reserved for Medicare’s naïve forecasters back in 1967.

- Peter J. Pitts is president of the Center for Medicine in the Public Interest and a former FDA associate commissioner. The opinions expressed are his own. -

The much ballyhooed White House summit on healthcare created no “aha” moments or Daily Show -worthy gaffes and was about as interesting to watch as Olympic curling.

President Obama was hoping, by force of will, intelligence and gravitas to both sway Republican lawmakers to his point of view (aspirational at best) while simultaneously demonstrating to the American people (and particularly American voters) that his proposal was a moderate one (arguable at worst).

From a communications perspective, he was presented with a classic Nick Naylor moment. The president didn’t realize the odds were 2-1 against. Not only did he have to prove he was right, he had to demonstrate the other side was wrong.

The GOP had an easier task — to have something constructive to offer, not get shrill (and yell “liar!”) or look at their watches. They succeeded.

House Minority Leader, John Boehner, rather than coming across as “Dr. No,” was the man with a plan – an easy-to-explain 6-point plan. Communications 101. The GOP were combative but collegial. Their sound bites were designed to generate nodding “me toos” across America. The Democrats were uncoordinated and visibly unhappy they were unable to paint themselves as the white knights of healthcare reform.

Obama and the Democratic leadership needed a dynamic event that would galvanize public opinion behind their call for immediate and comprehensive healthcare reform legislation. They needed a hard-hitting Olympic hockey game. But there were no stand-up body checks. Instead, the president looked like a professor grading papers and the whole enterprise looked and sounded like C-SPAN – the American equivalent of Olympic curling. Let the spinning begin.

- Peter J. Pitts, a former FDA Associate Commissioner, is Partner/Director of Global Health at Porter Novelli and President of the Center for Medicine in the Public Interest. The opinions expressed are his own. -

Late one recent wintry night in the midst of the Senate’s deliberations over healthcare reform, having worked hard on trying to reconcile the many swirling eddies of the current debate, I retired to bed for a few hours of fitful respite. That is until I was awoken from my solemn slumbers by a billowy translucent apparition who identified himself as the Ghost of Healthcares Yet-to-Come.

“Away ye spirit,” I intoned, “for I need my sleep and indeed see you for what you really are – a detail rep for Lunesta.” “Nay,” replied the apparition. “I am here to reveal to you alternate realities for healthcares yet-to-come.” And, with a wave of his spectral hand, appeared a magical black bag. “Look within,” he intoned. “And see how the future of American healthcare can unfold.” “Did you bring a pizza by any chance,” I queried? “Sorry, can’t do that any more,” the ghost replied. “Let our journey begin.”

And from inside his satchel he ceremoniously withdrew a heavy, leather-bound tome with a caduceus embossed on the cover. “What alchemist’s manual is this?” asked I. “It is,” whispered the spirit, “from the cabinet of doctors Pelosi and Reid. It is the final version of healthcare reform legislation.”

“Oh splendid visitor,” I pleaded. “May I gaze upon these pages and take notes for my blog? “NO!” the ghost sternly admonished. “You may look at the book, but may never read what is inside – just like members of Congress before the final vote.”

“Not fair,” said I. “Alas,” the specter replied. “Such is the future when healthcare legislation is focused primarily on politics rather than on advancing the public health.”

“But it need not be that way,” my navigator continued. “Let us move on an alternate future.” And with that he once again reached down into his black bag, revealing not a book but a Kindle. “Power it up,” he directed. “And see another future for American healthcare.”

And it was wondrous. A future of enhanced access, innovation and accelerated approvals. A future where, with appropriate FDA guidance, pharmaceutical companies actively engage in social media. A future where insurance companies reward its customers for medication compliance, weight loss, smoking cessation, and disease prevention. A future with a national standard for electronic medical records and e-prescribing. A future where the insurance industry offers high-quality health policies across state lines to the many millions of previously uncovered Americans at significantly lower costs. A future where reimbursement decisions are based on patient-centric concerns rather than 20th century cost-centered models. A future where physicians are compensated fairly by Medicare and Medicaid. A future where, through enhanced transatlantic regulatory harmonization, there is no “approval gap” for drugs, devices, or diagnostics. A future where the only doughnut hole question we consider is cream-filled or regular. A future where drug importation is a side show panel not in the U.S. Senate, but at Ripley’s Believe-it-or-Not.

“Can we peer into the future of the FDA,” I wondered.

“You’re such a wonk,” said my ethereal companion. “If you insist.”

And insist I did. As I browsed further into the magic Kindle I saw an FDA that’s both regulator in protecting the public health and colleague in helping to advance it via the Reagan Udall Foundation. I saw an FDA with a cutting-edge information management system. I saw an FDA that embraces predictability over ambiguity. I saw an FDA that understands the unintended consequences of early risk communications.

“Is such a future possible,” I asked.

“Indeed it is,” the eidolon answered. “It is possible if we believe.”

“If we believe in what,” I asked. “In Santa Claus?”

“No, intoned the wraith, “in the Non-Interference Clause. If we believe in free market competition and personal responsibility; in putting and keeping the patient in the center of every conversation; at long-term rather than short-term savings; in hard facts rather than political platitudes; in allies rather than enemies. If we believe that, in order to save lives, reduce costs, enhance quality, and deliver on the promise of robust health to all groups of Americans, all of the players in the health care debate – including government – must work together as a team, as a unit, as a public health defense force armed and ready to advance the public health.”

“How can we ensure this pathway,” I beseeched. “Let me tell you,” said the phantasm, “what my friend Ebenezer Scrooge once said to a colleague of mine. He said that men’s courses will foreshadow certain ends, to which, if persevered in, they must lead.”

“But,” I asked, “if the courses be departed from, the ends will change. Say it is thus with what you show me.” But, before he could answer, I saw an alteration in the Phantom’s hood and dress. It shrunk, collapsed, and dwindled down into a bedpost.